Effect of age and sex on lorazepam protein binding.
Effect of age and sex on lorazepam protein binding.
复制标题
年龄和性别对劳拉西泮蛋白结合的影响。
DOI：
10.1111/j.2042-7158.1982.tb04201.x
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发表时间：
1982
期刊：
影响因子：
--
通讯作者：
Greenblatt,DJ
中科院分区：
文献类型：
--
作者：
Divoll,M;Greenblatt,DJ
方法 15 名年龄在 19 至 84 岁之间的年轻志愿者和 15 名老年志愿者参加了先前描述的静脉注射劳拉西泮动力学研究（Greenblatt 等人 1979）。分布容积、消除半衰期和总清除率（游离加结合）是根据气相色谱法（Greenblatt et al 1978）在给药后最多 72 小时内多个时间点测定的劳拉西泮血浆浓度来确定的（见表 1）。劳拉西泮的游离分数（未结合百分比）通过改良的平衡透析技术（Woo & Greenblatt 1979）使用研究期间非禁食状态下抽取的单个样品测定。将重复的 1 ml 血浆样品掺入含有 2 nCi ml-1 的 [14C] 劳拉西泮（规格活性 101 pCi= 3.3 mg），并置于悬浮于 7 ml 等渗磷酸盐缓冲液（pH 7.4）中的透析膜中。将试管盖上盖子，并在 37°C 水平摇动 18 小时。每次运行中都包含来自合并样品的对照。血浆和缓冲液的等分试样与 15 ml Aquasol（New England Nuclear）混合，并在 Beckman 液体闪烁计数器中测定放射性。劳拉西泮的游离分数计算为缓冲相中的计数 min-I 与透析袋内部剩余血浆中的计数 min-I 的比率。重复样品之间的变异系数小于 3.5%，对照样品运行之间的平均变异系数为 2.7%。
MethodsFifteen young and 15 elderly volunteers aged 19 to 84 years participated in a kinetic study of intravenous lorazepam described previously (Greenblatt et al 1979). Volume of distribution, elimination half-life, and clearance of total (free plus bound) were determined based on lorazepam plasma concentrations determined by gas chromatography (Greenblatt et a1 1978) at multiple points in time for up to 72 h after the dose (see Table 1). The free fraction (percent unbound) of lorazepam was determined by a modified equilibrium dialysis technique (Woo & Greenblatt 1979) using a single sample drawn during the study in the nonfasting state. Duplicate 1 ml plasma samples were spiked to contain 2 nCi ml-1 of [14C] lorazepam (spec. act. 101 pCi= 3.3 mg) and placed in dialysis membranes suspended in 7 ml of an isotonic phosphate buffer, pH 7.4. The tubes were capped and shaken horizontally at 37" C for 18 h. A control derived from a pooled sample was included in each run. Aliquots of both plasma and buffer were mixed with 15 ml of Aquasol (New England Nuclear) and the radioactivity was determined in a Beckman liquid scintillation counter. The free fraction of lorazepam was calculated as the ratio of counts min-I in the buffer phase to that in the plasma remaining in the interior of the dialysis bag. The mean coefficient of variation between duplicate samples was less than 3.5%. The mean coefficient of variation between runs of the control sample was 2.7%.